Glutamine supplementation in major surgery and intensive care

Strong evidences suggest that glutamine (GLN) plays a key role of in several metabolic pathways and it has been recognized as an essential substrate for the appropriate function of many organs and the principal metabolic fuel for different rapidly dividing cells. Moreover, GLN is essential for cell metabolism because it is able to modulate gluconeogenesis, lipogenesis, anabolic processes, to preserve mitocondrial ATP levels and attenuate the activation of inducible nitric oxide synthase following ischemia, trauma and sepsis, and to maintain gut integrity. GLN supplementation might be important in stress conditions to maintain a stable tissue and plasma pool and improve the above pathways. The randomized clinical trials published so far evaluating GLN supplementation in elective surgical patients and in subjects receiving intensive care treatment - with few exceptions - suffer several important methodological limitations such as lack of sample size calculation, blindness, a priori definition of complications, intention-to-treat analysis, subgroup and post-hoc analysis, statistical underpower, and heterogeneous cohort enrollment. The protective effect of GLN supplementation on primary outcome measures, such as morbidity and mortality is not persuasive. The most methodologically robust trials evaluating GLN supplementation showed no benefits or even a trend to harm in specific subgroups. Up to now the available data do not support the routine use of GLN in elective surgical and in critically ill patients. Others large randomized trials are needed to clarify if there is any role for GLN supplementation in specific subgroups.